Neuroprotective actions of a histidine analogue in models of ischemic stroke

Tang, Sung-Chun, Arumugam, Thiruma V., Cutler, Roy G., Jo, Dong-Gyu, Magnus, Tim, Chan, Sic L., Mughal, Mohamed R., Telljohann, Richard S., Nassar, Matthew, Xin, Ouyang, Calderan, Andrea, Ruzza, Paolo, Guiotto, Andrea and Mattson, Mark P. (2007) Neuroprotective actions of a histidine analogue in models of ischemic stroke. Journal of Neurochemistry, 101 3: 729-736. doi:10.1111/j.1471-4159.2006.04412.x

Author Tang, Sung-Chun
Arumugam, Thiruma V.
Cutler, Roy G.
Jo, Dong-Gyu
Magnus, Tim
Chan, Sic L.
Mughal, Mohamed R.
Telljohann, Richard S.
Nassar, Matthew
Xin, Ouyang
Calderan, Andrea
Ruzza, Paolo
Guiotto, Andrea
Mattson, Mark P.
Title Neuroprotective actions of a histidine analogue in models of ischemic stroke
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 2007-05
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2006.04412.x
Volume 101
Issue 3
Start page 729
End page 736
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell
Language eng
Abstract Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions.
Keyword camosine analogue
ischemic stroke
lipid peroxidation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Created: Tue, 17 Nov 2009, 12:22:22 EST